A novel three-dimensional large-pore mesoporous carbon matrix as a potential nanovehicle for the fast release of the poorly water-soluble drug, celecoxib.

PURPOSE: A novel mesocellular carbon foam (MSU-FC) with a large pore size and a three-dimensional porous structure for the oral delivery of poorly water-soluble drugs was prepared. The goal of this study was to improve in vitro dissolution and in vivo absorption of celecoxib (CEB), a model drug, by means of novel carbon-based nanoparticles prepared from the MSU-FC matrix. METHODS: The MSU-FC matrix was synthesized by an inverse replica templating method using mesocellular silica template. A solvent immersion/evaporation method was used to load the drug molecules. The drug-loaded nanoparticles were characterized for morphology, surface area, particle size, mesoporous structure, crystallinity, solubility and dissolution. The effect of MSU-FC on cell viability was measured using the MTT conversion assay. Furthermore, the oral bioavailability of CEB-loaded MSU-FC in fasted rats was compared with that of the marketed product. RESULTS: Our results demonstrate that CEB incorporation into the prepared MSU-FC resulted in an approximately 9-fold increase in aqueous solubility in comparison with crystalline CEB. MSU-FC produced accelerated immediate release of CEB in comparison with crystalline CEB (pure CEB powder or marketed formulation) and the drug-loaded conventional mesoporous carbon particles. The relative bioavailability of CEB for CEB-loaded MSU-FC was 172%. In addition, MSU-FC nanoparticles exhibited very low toxicity. CONCLUSIONS: The MSU-FC nanomatrix has been shown to be a promising drug delivery vehicle for improving the dissolution and biopharmaceutical characteristics of poorly water-soluble drugs.

Development of novel mesoporous nanomatrix-supported lipid bilayers for oral sustained delivery of the water-insoluble drug, lovastatin.

The purpose of this study was to investigate the effect of a core/shell structured nanocomposite, mesoporous nanomatrix-supported lipid bilayer (MN-SLB), as an oral drug nanocarrier, on the dissolution behavior and in vivo absorption of a water-insoluble drug, lovastatin (LOV). The formulation strategy was based on the use of drug-loaded mesoporous silica as the core for the fusion of liposomes. Field emission scanning electron microscopy (FESEM), cryogenic transmission electron microscopy (Cryo-TEM) and nitrogen adsorption were used to systematically characterize the drug carrier and drug-loaded MN-SLB formulation, confirming the successful inclusion of LOV into the nano-pores of MN-SLB. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) confirmed that the incorporated drug in the carrier was in an amorphous state. An in vitro dissolution study showed that LOV-loaded MN-SLB exhibited a sustained drug release behavior. Compared with the LOV-loaded mesoporous silica particles, LOV-loaded MN-SLB markedly suppressed the burst release. Furthermore, the pharmacokinetics and relative bioavailability of the LOV-loaded MN-SLB formulation was studied in beagle dogs after oral administration and using a commercially available immediate release formulation (Sandoz Lovastatin®) as a reference. It was found that the relative bioavailability of LOV and LOV ß-hydroxy acid (LOVA) for the LOV-loaded MN-SLB formulation was 207.2% and 192.1%, respectively. In addition, MN-SLB exhibited negligible toxicity against Caco-2 and HT-29 cells in cytotoxicity assays. The results of this study indicate that the MN-SLB nanocomposite is a promising candidate as a novel oral drug delivery nanovehicle for controlling the dissolution rate and improving the oral absorption of water-insoluble drugs.

Highly ordered mesoporous carbon nanomatrix as a new approach to improve the oral absorption of the water-insoluble drug, simvastatin.

Three different kinds of highly ordered mesoporous carbon (HMC) matrices with different morphologies (hexagonal, spherical and fibrous), particle sizes (700 nm, 400-900 nm and 1-4 µm) and pore diameters were compared as drug carriers for a model drug, simvastatin (SIM). The physicochemical properties of the SIM-loaded composites were studied using field emission scanning electron microscopy (FESEM), specific surface area analysis, differential scanning calorimetry (DSC), wide-angle X-ray scattering (WAXS), HPLC, solubility measurement and dissolution testing. Furthermore, the oral bioavailability of SIM-loaded SHMC (spherical HMC nanomatrix) in beagle dogs was compared with that of the reference formulation (Zocor®). The results obtained showed that SIM molecules are encapsulated in a noncrystalline state due to geometric confinement in the nanopores of HMC. In vitro dissolution testing showed that the dissolution rate of SIM released from monodispersed SHMC was significantly faster compared with that of crystalline SIM and other SIM-loaded composites. In addition, in vivo bioavailability study demonstrated that the relative bioavailability of SIM and SIM ß-hydroxy acid (an active metabolite of SIM) for SIM-loaded SHMC formulation was 138.42% and 163.55%, respectively. In conclusion, monodispersed SHMC appear to be a more promising candidate as a new oral drug delivery vehicle providing a rapid drug release and enhanced oral bioavailability.